Search Results (5)

Quorum-sensing (QS) is a regulatory mechanism in bacterial communication, important for pathogenesis control. The search for small molecules active as quorum-sensing inhibitors (QSI) that can synergize with antibiotics is considered a good strategy to counteract the problem of antibiotic resistance. Here the antimicrobial labdane diterpenoids sclareol (1) and manool (2) extracted from Salvia tingitana were considered as potential QSI against methicillin-resistant Staphylococcus aureus. Only sclareol showed synergistic activity with clindamycin. The quantification of these compounds by LC–MS analysis in the organs and in the calli of S. tingitana showed that sclareol is most abundant in the flower spikes and is produced by calli, while manool is the major labdane of the roots, and is abundant also in the leaves. Other metabolites of the roots were abietane diterpenoids, common in Salvia species, and pentacyclic triterpenoids, bearing a γ-lactone moiety, previously undescribed in Salvia. Docking simulations suggested that 1 and 2 bind to key residues, involved in direct interactions with DNA. They may prevent accessory gene regulator A (AgrA) binding to DNA or AgrA activation upon phosphorylation, to suppress virulence factor expression. The antimicrobial activity of these two compounds probably achieves preventing upregulation of the accessory gene regulator (agr)-regulated genes. Full article

Anoxybacillus amylolyticus is a moderate thermophilic microorganism producing an exopolysaccharide and an extracellular α-amylase able to hydrolyze starch. The synthesis of several biomolecules is often regulated by a quorum sensing (QS) mechanism, a chemical cell-to-cell communication based on the production and diffusion of small molecules named “autoinducers”, most of which belonging to the N-acyl homoserine lactones’ (AHLs) family. There are few reports about this mechanism in extremophiles, in particular thermophiles. Here, we report the identification of a signal molecule, the N-butanoyl-homoserine lactone (C4-HSL), from the milieu of A. amylolyticus. Moreover, investigations performed by supplementing a known QS inhibitor, trans-cinnamaldehyde, or exogenous C4-HSL in the growth medium of A. amylolyticus suggested the involvement of QS signaling in the modulation of extracellular α-amylase activity. The data showed that the presence of the QS inhibitor trans-cinnamaldehyde in the medium decreased amylolytic activity, which, conversely, was increased by the effect of exogenous C4-HSL. Overall, these results represent the first evidence of the production of AHLs in thermophilic microorganisms, which could be responsible for a communication system regulating thermostable α-amylase activity. Full article

Numerous gram-negative phytopathogenic and zoopathogenic bacteria utilise acylated homoserine lactone (AHL) in communication systems, referred to as quorum sensing (QS), for induction of virulence factors and biofilm development. This phenomenon positions AHL-mediated QS as an attractive target for anti-infective therapy. This review focused on the most significant groups of plant-derived QS inhibitors and well-studied individual compounds for which in silico, in vitro and in vivo studies provide substantial knowledge about their modes of anti-QS activity. The current data about sulfur-containing compounds, monoterpenes and monoterpenoids, phenylpropanoids, benzoic acid derivatives, diarylheptanoids, coumarins, flavonoids and tannins were summarized; their plant sources, anti-QS effects and bioactivity mechanisms have also been summarized and discussed. Three variants of plant-derived molecules anti-QS strategies are proposed: (i) specific, via binding with LuxI-type AHL synthases and/or LuxR-type AHL receptor proteins, which have been shown for terpenes (carvacrol and l-carvone), phenylpropanoids (cinnamaldehyde and eugenol), flavonoid quercetin and ellagitannins; (ii) non-specific, by affecting the QS-related intracellular regulatory pathways by lowering regulatory small RNA expression (sulphur-containing compounds ajoene and iberin) or c-di-GMP metabolism reduction (coumarin); and (iii) indirect, via alteration of metabolic pathways involved in QS-dependent processes (vanillic acid and curcumin). Full article

Quorum sensing (QS) is a phenomenon of intercellular communication discovered mainly in bacteria. A QS system consisting of QS signal molecules and regulatory protein components could control physiological behaviors and virulence gene expression of bacterial pathogens. Therefore, QS inhibition could be a novel strategy to combat pathogens and related diseases. QS inhibitors (QSIs), mainly categorized into small chemical molecules and quorum quenching enzymes, could be extracted from diverse sources in marine environment and terrestrial environment. With the focus on the exploitation of marine resources in recent years, more and more QSIs from the marine environment have been investigated. In this article, we present a comprehensive review of QSIs from marine bacteria. Firstly, screening work of marine bacteria with potential QSIs was concluded and these marine bacteria were classified. Afterwards, two categories of marine bacteria-derived QSIs were summarized from the aspects of sources, structures, QS inhibition mechanisms, environmental tolerance, effects/applications, etc. Next, structural modification of natural small molecule QSIs for future drug development was discussed. Finally, potential applications of QSIs from marine bacteria in human healthcare, aquaculture, crop cultivation, etc. were elucidated, indicating promising and extensive application perspectives of QS disruption as a novel antimicrobial strategy. Full article

Quercus cortex (Oak bark) has been used in European folk medicine since medieval times for treatment of diarrhea, stomatitis, pharyngitis and skin inflammations. Its antimicrobial activity is a well-known therapeutic property of oak bark, and its novel anti-quorum sensing (QS) ability has also been described recently. In this study, we examined the bioactive compounds of Quercus cortex extract and compared their direct antibacterial and regulatory anti-QS effects against Chromobacterium violaceum CV026 in a biotest. Evaluation of the original Quercus cortex extract showed weak antibacterial and prominent anti-QS activities that were retained and completely restored when the samples were dried and re-hydrated. The one-step liquid chromatography result indicated that the anti-QS activity might be determined by hydrophobic compounds; however, the subsequent reverse phase high performance liquid chromatography led to dissipation and loss of the activity. The gas chromatography–mass spectrometry gave excellent resolution between a majority of the compounds. Based on this result, 10 of the 35 identified small molecules were selected for further screening. The subsequent investigation indicated several compounds determined both the antibacterial and anti-QS activities of the Quercus cortex extract. Direct antibacterial activity was shown for 1,2,3-benzenetriol and 4-propyl-1,3-benzenediol, while sub-inhibitory concentrations of these compounds led to anti-QS effects. Five compounds: 4-(3-hydroxy-1-propenyl)-2-methoxy-phenol; 3,4,5-trimethoxyphenol; 4-hydroxy-3-methoxybenzaldehyde; 7-hydroxy-6-methoxy-2H-1-benzopyran-2-one and 2H-1-benzopyran-2-one were characterized as QS inhibitors independent of any effect on bacterial growth. Biologically relevant concentrations of each single component showed weak activity only while reconstruction of the small molecule composition derived from the Quercus cortex extract provided comparable complementary activity against C. violaceum CV026 in the biotest as the crude extract. Full article